We are considering car rental out of Rome and stopping in Assisi on way to lodging 30 minutes outside of Florence.
Any suggestions re: viability of this option?
Rome Assisi Florence
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Perfectly viable.
We have rented cars in Rome several times - just pick a location with easy access to a major road heading in your direction.
have not booked Florence region accomodations. Any suggestions, 3 adults, one room?
Another option is to take a train to Foligno and rent the car at the Foligno train station. Depending on the day of the week and time of day, you could likely train to Foligno faster than you could drive there. Faster trains take 90 minutes, and the drive would likely take over 2 hours. The train station in Foligno is a very short distance off the main road to Assisi (about 30 minutes farther north). Depending on where your lodging outside of Florence is located, it will probably be another 2 hours of driving after Assisi.
FYI, the rental agency office at Foligno is closed from 12:20 p.m. to 3:30 p.m. Mon-Fri, closed Saturday afternoons and all day Sunday.
As to the "Florence region accommmodations," what do you want to be able to see/do from that location (i.e., where do you want to explore?) Do you want to be IN a city or town? At an agriturismo? What's your budget?
IMHO the reason to rent the car in Rome is that the major offices are open every day and full business hours. Much more convenient than trying to match your schdule to a part-time office. (And do realize that business offices in Italy tend to have very flexible hours - to their benefit.)