We are planning our next trip to Europe. We plan on flying into France or Amsterdam (to visit friends) Then to Paris, Marselles and drive the coast around to Italy ending and departing from Rome. We have 21+ days. Is this a reasonable amount of time and is auto rental from France with a drop off in Rome possible. We will get a train pass before we go for Netherlands/France/ Germany. Any advise is greatly appreciated.
The time will work fine if you don't spend seven evers with your friends or forget to leave Paris. The killer is going to be the second-country drop-off fee. Make a couple of test runs on a car rental site: France to France for x-days, then France to Italy for the same period. See if you want to swallow it. What I'd probably do is get the car as you leave Paris, drop it as close to the border as you can, take the shortest train ride you can figure out, then get another car. The whole operation probably wouldn't kill much more than half of a day. The train pros can give you an idea of the spots to do it.
If you make it a lease, the drop off fee is significantly less than a rental drop off fee (or was when I did it). We picked up in A'dam and dropped in Rome. Even with the pick up/drop off fees (any location outside of France), it was still a great deal. The biggest hassle is what to do with your car when you are in a city - find a safe and inexpensive place to park it for your stay - other than that it works well.
You can easily check out your prices and options at autoeurope.com. If you're going to want the car 17 days or longer, be sure to check out the lease/buyback option, which as Brad says can be a great deal.
surely you won't need both a train pass (useful for LOTS of riding long distances) and a long car rental? Your itinerary didn't say anything about Germany but then you said you will have a pass for there?
What is your train itinerary for the Netherlands, France, and Germany? If you can commit to specific departure dates and times and book well in advance, pont-to-point discount fare tickets often are cheaper than a railpass.
All the other posters have given excellent advice which I certainly endorse. However, I am not clear why you need to rent a car at all. Certainly a car will be a huge nuisance in Amsterdam and Paris. And since you are headed for Italy, why detour to Marseilles? Why not take a TGV direct to Nice on the coast in 5 hours? From Nice you can easily do the coast without a car, and the train from Nice to Genoa and Genoa to Rome is pretty easy. And I don't even want to imagine driving in Rome. It's bad enough being a pedestrian there. If you are going to have a railpass (I assume you meant Benelux-France-Italy), why rent a car at all? If you plan on spending lots of time in rural Provence or hill-town Italy, sure....but your post seems to suggest a trip focused mainly on great cities where a car is not needed or even desirable.