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Many years ago someone did do it, but it's really not practical. As I recall the water pump hub is in the same space as the radiator, so it does take a lot of work and relocation of critical pieces to force it to fit. Best to stick with the 223 for an OHV 6 unless you just have to have the 300 for bragging rights. Just know you'll be in for some work, if not a fight. The parts are out there for the 215/223 engine family to drop in, but they're 52 only as that was the first year for that engine, and the only application for this bodystyle.
I believe Greg Rogers from Michigan has a straight 6 in his 56 F100. The donor truck was from the 80's. I believe Greg's truck is running and driving. If I'm remembering right, Greg might be a mechanic by trade, which might be something to consider. Just because Greg could do it doesn't mean it would be a good project for just anyone.
That's good info, Jim. I didn't remember who did it or put it into what. But just to clarify for the benefit of the uninitiated, the 53-56 engine compartment is considerably larger than the 48-52. So what might fit in the later truck may still be a struggle, or more of a struggle, in the earlier ones. Take careful measurements and know what you have to cut/trim/modify before diving in head first. It may save a lot of headaches down the road.
Worked on the 65-72 Chassis all my Life 35 plus years, and built my share of Engines, with I-Beam Swaps, and Welding, Novice I'm not. But wanted some advice and Thank you Gentlemen for it. I have a 302 option just thought the 300 would be something Different. Thanks