Way too little data yet to give one answer. Der/pulley alignment (bent hanger or pivot bolts and cross threaded mounting bolt being typical). Limit screw settings. Wear of chain, cog teeth, pully wheels all contribute to noise, worse over time and lack of maintenance. Just a few aspects I would look for.

BTW when you say "lowest gear in back" do you mean the largest cog/closest to the spokes, or the outer one, smallest cog? Have you changed things lately? The B screw doesn't rotate or it does but the der does nothing different?

Without good photos or an in person hands on it's hard to eliminate any possibilities. Andy.