Am not familiar with this route designation but I assume this is what many call sailing down I-65 IE sail east to longitude 65W and turn south.
My opinion, based on a few trips to the VI from FL, there's no easy, perfect answer.
Almost any time of year you make this trip will offer some pluses and minuses. Too early in the fall and you are still in hurricane
season. Too late in the fall and you are at risk of cold fronts (nor'easters that moved south) and the strong winds associated with that system. Some years the seasons overlap so you can get early fronts and/or late hurricanes.
If you're leaving from south FL you are, in my opinion and experience, too far south to benefit greatly from the outside route. In south FL you are already in the trade
winds zone and trying to sail east, whether you head
outside or work through the islands you will be beating into the wind
, waves and current
. Best route to minimize beating to weather
is to depart from further north. Morehead City
NC is a common jumping off point. However the same weather
If you have the time, my preference is to go through the islands and enjoy the trip. Take your time, pick weather windows and island hop.