Three-dimensional covalent organic frameworks (3D COFs), a class of highly porous crystalline polymers, have exhibited great potentials in many applications. However, the reported topologies of 3D COFs have been limited to high-symmetry crystal systems, which significantly hindered the development of such functional materials. Herein, we demonstrate the first construction of four highly crystalline orthorhombic 3D COFs with an unprecedented fmj topology, based on judiciously choosing rotatable monomers. Notably, the square monomers in the unit cell of the fmj topological network adopt three different conformations, resulting in a highly complicated 3D network. Moreover, an isomeric pair (3DCOF-CN and 3DCOF-NC), differing only in the orientations of -C=N-bonds, exhibit distinct optoelectronic properties, protonation abilities, and photocatalytic activities, which is the first time to reveal such isomeric effects in 3D COFs. Particularly, a difference of 32-fold in photocatalytic hydrogen evolution rate was observed for the two isomers, with one achieving a superb rate up to ~31.1 mmol h