I don't know if the results are due to the powder or the bullets or both because you changed both at the same time. If only the powder were changed then at least it would reveal if the groups were the fault of the bullets or not.
Either way, I suspect that because those 375 grain bullets can damage big game in ways that the 250 grainers can't, that the perfection of the overall group isn't quite as important as the terminal performance of the shot.
The game kill zone would most likely be larger than your target, the barrel may be cooler, better performing powder may be selected and the scope may also be sighted in to match that bullet's trajectory at longer range. I think that you may have even shown us better groups fired with that same bullet from a different rifle before.
And even then, if you can put that same bullet in the chest of a big game animal I'd bet that the bullet would do its job in a way that would more than make up for the lack of MOA accuracy.
And maybe that bullet and/or powder just won't shoot satisfactorily from that rifle. So you tried it and weren't happy with the results. If the weather or powder were different, then maybe some adjustments could be made to improve accuracy.
But I'm convinced that shooting groups isn't quite as important as where the first shot out of a cold clean barrel lands and then what it does to an animal.
Knowing your accuracy expectations, you probably wouldn't select that combo. anyway. But if you absolutely had to, I'll bet that if anyone could that you would be able to find a way to make it work.