I used to shoot a lot of .22 metallic silhouette with my Kimber M82 in .22 LR. The ram target (shot at 100 yards) is almost exactly the size of a squirrel.
I zero a scoped .22 at 50 feet and check at 75 yards -- with high velocity ammunition, it will be dead on at the latter range. By holding a tad low, shorter shots are easily made. At 100 yards, I would perch the squirrel on the top of the thick lower crosshair. I have killed many late-season squirrels at that range with that rifle.