Are all the guidebooks correct on routes?

I think it would be better to fit CT in between Siena and Assisi or after Venice ; therefore ending in Rome and flying out of Rome.
Less backtracking and Flying out of Milan from the CT likely means a hotel overnight on the last night closer to the Airport or in Milan to make that work.

I think I would rent the car when leaving Venice and return it when done with your stay in Siena.
Or if going from Venice to the CT, rent the car in La Spieza after your 3 nights in CT, stop in Pisa and then drive onward to your Siena farm stay and drop the car off when done with Siena area.

if you have to cut an area for more time in another, I would cut out the Assisi area (though I have never been) Basically I have cut it out personally in similar situations.

Hi, mreynolds. The CT between Siena and Assisi? I'm looking at a map wondering how that would work well?

I would do the trip a little different.
Fly into Pisa (from another European gateway city, like London). Take the train up to LaSpezia and a local train into the Cinque Terre.
Then take the train back to LaSpezia and on to Venice.
Then take the train back to Florence and pick up a Hertz rental car. (They'll give you directions to avoid ZTL's)
Visit your agriturismo around Siena and do day trips to the hilltowns like Volterra and see Chianti.
It's maybe 90 minute drive down to Assisi. Turn your rental car in at Orvieto's Hertz location across the street from the train station. It's a 70 minute train ride into Rome Termini.
Fly home from Rome FCO.

The biggest reason guide books use that route is to avoid back-tracking. Nor really that big of a deal - Rome back to La Spezia is about 4 hrs on the train.

Good suggestions! Thinking about the drive from CT.... Better/more scenic from La Spezia > Pisa > (Volterra, time permitting) > Siena farm stay or from Florence > SR 222 thru Chianti region to Siena farm stay?

Was more trying to revise your plan so your last stop was not CT with a flight out of Milan

Highways in Italy are as pretty as highways in the US but would still take them for far journeys to save time.
To and from La Spieza for example.

The scenic routes south of Siena are very pretty indeed, I have not been to the Chianti region but suspect there are scenic drives in that area as well. Just south of Siena is the Crete Senesi area which is nice, scenic and remote feeling further south of that is the Val D'Orcia area which is even nicer, more scenic but less remote feeling.

Hi, mreynolds. You are being very helpful. Honestly, this all started - and will center - around having a great farmhouse stay in a beautiful area of Tuscany. With that in mind, my initial thought was to have two farmhouse stays just to experience good food and the countryside in two slightly different areas. Even though the Siena and Pienza farm stays were only one hour from each other I was thinking of doing that, but most said I needed to choose one area and simply day trip to the other. It seems logical to go to San Gimignano, Volterra, Chianti, (Assisi, perhaps) from the Siena area. From the Pienza area, it seems logical to go to Montepulciano, Montalcino, (Orvieto, perhaps). You've obviously been there -- I'd love your opinion.... A farm stay just outside of Siena, a farm stay in the heart of Val d'Orcia or split the time? The rest of this particular trip will center around this Tuscan stay, really. Thanks, again, for sharing your experiences.

The reason why CT is rarely if ever at the end is because it is more efficient to end the trip in the city you fly back from. There are no airports near CT.

I visited Tuscany under a similar pretense... wanting to see the beautiful countryside.
What I didn't really grasp until there is how cool the small hilltowns themselves are.

Towns like Pienza, Montepulciano, Montalcino, etc... I wouldn't want to stay at a farm stay when I could stay in a cool little town like Pienza and be able to reach the farm countryside within a few minutes by car plus have a commanding view of it from most anywhere in town along with the conveniences a town brings like cafes, restaurants, shops, etc...
The town of Pienza is really tiny, so it feels nothing like a city.
I actually preferred Montepulciano but Pienza is smaller so makes logistics a little easier to go back and forth on trips to the countryside.

I have never been to Chianti/Greve ; I am sure the small towns there are great as well. I don't think the scenery there is as nice as Val 'Orcia but if you want to visit wineries it may better or at least as good.

Assuming you are coming for the scenery, which should be ideal in May by the way with the flowers in bloom and the grass super green.
I found the countryside between Pienza and San Quirico to be the most beautiful compared to anywhere else.
You will find that 90% of the postcards you see of Tuscany are from this little tiny area, only a few miles big and some major scenic sites are practically right next to each other. (Belvedere Farmhouse, Madonna Chapel, Gladiator Road, Famous Driveways lined with Cypress, the couple famous Cypress patches you may have seen, etc...)

Siena was great too, but enjoyed that more for the medieval city it is rather than the countryside there.
I did spend some time driving around countryside closer to Siena and it is cool and very different. I also think the towns of San Gim and Volterra are more than worth your time if you can fit them in.
There really is so much to see and do in Tuscany it is hard to fit everything in.

I am not sure if you need 2 bases for the 2 areas to be explored, depends how much you like to drive vs. how much you like to stay at a base vs. checkin/checkout, we based out of Florence and then Pienza which worked out well and much different stays.

Not trying to talk you out of a farm stay if you have your mind set on it, just giving you my impression that the farm houses are all fairly remote with nothing around within walking distance. I would get bored after dark.

And see, I felt the opposite. I was just in that area a couple of weeks ago - Pienza, Montalcino, San Quirico, Monticchiello, etc. . . .and I would have loved to have stayed out in the gorgeous countryside-- and gone into town when we wanted to.

It all depends what YOU are most interested in!!!