The F250/F350 longbeds are horrible to ride on concrete highways when unloaded. They shake/resonate horribly between 70-79mph but faster and slower speeds alleviate the problem.
Also, there are thousands of posts on Ford Super Duty forums since 2000 with a persistent rear end hop at 45mph that has plagued the Fords and is likely due to too much flex in the frame.
Rear End Hop
Rear end bounces @ 40-45 MPH - Ford Truck Enthusiasts Forums
Wheel hop/ back seat shake - Ford Truck Enthusiasts Forums
I have a '15 F350 172" wheelbase with longbed. It rides like a dream on asphalt highways but segmented concrete gives my kidneys a jarring and my 5'1" DW needs a 5 point harness so as not to hit the roof.
500-800 lbs of dead weight in the truck bed helps smooth things out when unloaded.
When towing, the issue is not a problem. We often unhook when we camp and like to explore new areas with our truck so using the truck only when loaded is not an option.