All of my long range rigs shoot symmetrical 3 shot groups. I use 3 shot groups for all of my hunting rifles. By symmetrical I mean that I might shoot a 3 shot group and the hits may be at 12 o'clock, 4 o'clock and the third at 8 or 9 o'clock. The next time the same symmetrical 3 shot group may have the shot hits reversed etc. etc.
I sight my stable, long range rigs using a zero based on the center of the 3 shot group. You can see how, if you picked a single cbs, your potential zero might be a little off because shots 1-3 don't always hit in the same order, in the same place, but by using the center of the group then I am sighted for the average CBS from my average group.
The groups from my main dedicated long range rig run under 1" typically at 300 yards under ideal conditions so the difference in the 3 shots of the group is pretty small.
You can see how that if you had a gun that only held 3"-6" at 300 yards that you may have problems at looong range. The only way to eliminate entirely the difference in your poa and your poi would be to shoot only one hole groups at all ranges.