Goldin Auctions is offering what they claim to be the last autograph President Kennedy ever signed.  On their website, it's described as follows:

Offered is this file card that features a small drawing of Kennedy that reads: “Pictures of J.F.K. sketched on Nov 22 1963 at Prayer Breakfast in Forth Worth, Texas”. President Kennedy has signed this carde underneath the picture drawing in pencil. This card measures 3 x 5 inches and is unframed. Given the events of that day, it’s more than likely that this item might have been the last ever signature of Kennedy. This item comes with a LOA from Steve Grad of Beckett Authentication.

And here it is...

If the facts as stated are true, then this would indeed be the last known autograph JFK signed.  We do know of at least one other autograph he signed that day, on the front page of a Dallas newspaper...

...but according to the description by Heritage Auctions, who sold it for $38,837.50 in 2009, he signed it on his way to the speech (whereas, according to the description, the one Goldin is auctioning was signed after the speech).

Links:

Goldin Auctions listing (2017)

Heritage Auctions listing (2009)