1898, Henry James, The Turn of the Screw, Courier Dover Publications, published 1991, →ISBN, page 72:
No evening I had passed at Bly had the portentous quality of this one; in spite of which—and in spite also of the deeper depths of consternation that had opened beneath my feet—there was literally, in the ebbing actual, an extraordinarily sweet sadness.
In spite of is at once three words and one preposition; as may be seen in the 1898 quotation above, it is not separated during preposition-stranding (hence “in spite of which […]”, never *“of which […] in spite”), but it may sometimes be separated by an adverb (as in “in spite also of”).
The phrase is often misused where regardless of would be appropriate.