Is it possible to replace the main bearings in a 2001 Escape 3.0 with the engine in the vehicle? Thanks in advance!

 

If you can get the oil pan off, and the 'girdle' bearing cap carrier, you can the remove one main bearing cap at a time, or loosen them all to let the crankshaft drop a bit, and then rotate the top shell out, rotate a new top bearing shell in place, replace the bottom, both pre-lubed well, and go on to the next. So, I'd say, yes, you can.
I know of nothing impeding except the exhaust / converter assemblies and Y-pipe. Possibly just the Y-pipe would need to be dropped.
FWIW, I would suspect the rod bearings to have more clearance before the mains. Reason being that the rods are generally fed from the mains, so the mains will have more lube than the rods during their 'lifetime', and thus should wear less.
Before doing the replacement, I would check the clearance and condition{copper showing or not} and the condition of the journals. If you don't have scored journals, you should be ok replacing the inserts.
tom