It is nearly impossible, but not absolutely impossible. Depressing the clips on the harness connectors in that tight space is a real bear sometimes. I found that after pulling the nut that holds it in place (on the top of the block), tilting it out as much as possible is the only reasonable way to access the back. Getting the connectors back on is every bit as much of a pain in the ass.
Important note: If replacing the block, be absolutely certain you get one for your year of truck (i.e. facelift vs. pre-facelift). The wrong year block will fit in fine and connect to the harness, but will really screw things up with your truck's electrical system. Feel free to ask how I know this. There is also a wait time when installing a new block before you can turn the key to "Start" while the light in the gauge cluster stays illuminated. From what I gather, the computers and fuse block need to re-establish their connection during this time. Once the block is in and battery reconnected, turn key to "Run" and wait a few min for the light to go out, then the truck will be ready for use again.