Yes it can IF the load capacity is sufficient. As hypoxia says, the 11R22.5 has a somewhat lower load rating. It is usually sufficient to replace a 295/80 on the rear (drive) axle where weights run lower, but maybe not enough for a front axle (only two tires to share the load). I've been running 11R's in place of 295/80 on my rear axle for 4 years now.
If you need more weight capacity, a 12R will usually fit as well, but using it on the back axle throws the speedometer off a bit.
Former owner of 2004 American Tradition
Home is in the Ocala Nat'l Forest near Ocala, FL