My '65 with a 250 gets 20 mpg with a Saginaw 4-speed & stock 3.73 rear-end. I never exceed 60 mph, and drive 45 most of my 21-mile commute. It's pretty stock, though rebuilt (.030 over) several years ago. It'll pull a trailer with a car on it no problem, and is a grin every time I get in it.
I say: "Go for it!"

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If you can't fix it with a hammer and screwdriver, you need a bigger hammer.
1965 Chevy C10