We have a 2021 F250 7.3 gas with 4.30 rear which we ordered to pull a 295RL. We did two big trips this year. Maryland to Florida (2200 tow miles) and Maryland to Yellowstone (4700 tow miles). Heading to FL via I95, only one stop for gas did we have to leave and go to a different gas station. Heading to Yellowstone there were a couple of situations where we just needed to wait for an end gas pump but for the most part no issues.
Considered diesel but being from MD with no major mountains went with the gas and 87 octane. There was maybe one time heading into Yellowstone via the East gate from Cody where you could say the diesel would have been worth it. I can tell you that I was very impressed with this setup heading into and out of the mountains. With tow haul mode engaged had no issues going up or coming down those mountains (one exception mentioned). Regarding downhills, tapped the brakes and the tranny downshifted and worked great. Yes, RPMs were screaming but not near redlining.
No problem cruising 65mph and occasionally 70mph across South Dakota. Typically 8.5mpg towing at 65mph. Yes, I as well wish the tank was bigger at times but for both of these trips we traveled 350-400 miles a day. One stop for a fill-up (started looking with 100 miles to empty) and bathroom/lunch stop. Once we setup for camp, went and filled up the truck for the next day.
Hope this helps