[POWERSTROKE]

Both of my 300-6 powered Ford F-150's had 3.50/3.55 final axle ratio with 235-75R-15 tires, the engines had to wind up pretty good, 2500-2600 to run 65 mph which REALLY hurt mpgs. One had a little Carter YF-1 1 barrel carb, other was factory EFI and supposedly made around 20 hp more than the carbide truck. Carb =125 hp, EFI = 145. Both got around 14 mpg if I drove 55-60, try to run 65-70 and get 11. The carb had ALL kinds of bad habits, I ended up converting it to manual choke which reduced but didn't eliminate them all. The EFI was much better. A co-worker with a similar EFI truck and a 4 speed over-drive Trans claimed 17-18 mpg vs my 14.
SON had a '93 F-150 LIGHTNING pickup, 351 Windsor with higher flowing GT-40 induction system good for 20-30 added HP, 4.10 final drive ratio, 275-60R-17 tires, and the E4OD auto Trans had a .71:1 overdrive ratio. I got 14 mpg commuting to work one week, SON would draft other cars & trucks and get 18 mpg.
The V-6's are a low end torque engine, I wouldn't go any lower than a 3.00 axle ratio, but without and overdrive gear in your transmission a 3.23 or 3.55 ratio would be good.
My 2018 RAM 1500 has 3.92 axles, cruises 80 mph at 2000 rpm in 8th gear, a .67:1 ratio, 7th is .87:1, 6th is 1:1. it has 275-60R20 tires. I get 15 mpg around town and 17-18 mpg on Interstate. Towing it pulls like my '96 F250 Diesel did but the MPG is less. But it takes gas to make 395 hp. ENGINE MASTERS did an episode on the latest 5.7L Hemi, They were impressed, I am too.