The problem is that Access WILL NOT do more than 255 fields in a given table.
The next comment will sound a bit arrogant, but it is not intended that way. There is NO WAY that your 300-column spreadsheet is properly normalized. And if it is, then you shouldn't be using Access anyway. So the FIRST issue is really one of designing how things should appear.
I think you would get greater benefit if you gave us SOME details about what is in that spreadsheet. SOME details - but not every little detail. Give us an overview of the problem you are addressing by building a database, not the problem you are having while trying to build that database. (We already know the latter problem.)