I hear if you eat the hole first, that takes up all the calories for the donut and sends them into a spatial vortex…
I think that’s how I said it, anyway… 
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Rust, 'ey…
The most common solution is Bondo (after removing rust.)
The easiest solution is Fiberglass Patch Kit+Bondo (after removing rust.)
If you’ve got an entire machine shop in your garage, sure fabricate some metal.
If you don’t have a steady hand, about your best option is to replace your Quarter Panel(s). They’re like $150 each for my truck. All you need is a drill, a bit, and a welder. but you may find it’s easiest to remove the bed first and then you’d need some sockets and buddies or a crane.
Yeesh, some of these people are annoying.
Lies!
The easiest solution for a pickup bed that won’t require you to go back in 3 years and do the job again is to find a rust-free pickup, wrecked somewhere other than the bed, in a junkyard and grab the bed.
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Clearly you’ve never restored a vehicle.
You’d spend more than an hour simply picking up a new bed…let alone finding one. Replacing the quarterpanels with an aftermarket rust resistant coating is going to be much easier…but then again, you can also repair the current panels, even cheaply, and spray on some rust resistance.
Clearly you don’t read the second half of sentences. Your way is easiest if you’re cool with doing the job over and over again. My way is easiest if you want to do the job once and then get on with your life.