We have revealed the photoreaction mechanism for the single-crystal-to-single-crystal transformation of bis(3,4,5-trifluorobenzyl) (E,E)-muconate (1) to the corresponding dimer. The [2 + 2] photodimerization randomly occurred in the columnar assembly of monomer molecules in the crystals of 1, followed by the formation of a trimer. The photoreaction was directly monitored by an X-ray single crystal structure analysis as well as the product analysis by NMR and MS spectroscopies.