Learn Italian: Questa riserva è grandissima e bellissima. - This sanctuary is very big and very beautiful.

Yes, santuario exists, but it almost exclusively refers to a religious shrine, temple, or holy place. When talking about a wildlife sanctuary, nature reserve, or protected land, Italian uses riserva (often riserva naturale) or sometimes oasi.

We learned that grande has a special superlative form, massimo. Why use grandissima here instead?

Both forms exist but serve different purposes. Grandissimo is the regular absolute superlative and means 'very big' or 'huge' in a literal, physical sense, which fits this nature reserve. Massimo is the irregular form meaning 'maximum', 'highest', or 'greatest' (e.g., il massimo sforzo for 'the maximum effort'), which wouldn't make sense for describing physical size here.

Is there a difference in tone between saying molto grande e molto bella versus grandissima e bellissima?

While both mean 'very big and very beautiful', the -issimo suffix (the absolute superlative) is much more expressive and frequently used in Italian to show enthusiasm. Using grandissima e bellissima flows better and sounds more natural than repeating the word molto twice in the same sentence.