Dynamic 3D covalent organic frameworks (dynaCOFs) have shown concerted structural transformation and responses upon adaptive guest adsorption. The multivariate (MTV) strategy incorporating multiple functionalities within a backbone is attractive for tuning the framework flexibility and dynamic responses. However, a major synthetic challenge arises from the different chemical reactivities of linkers usually resulting in phase separation. Here, we report a general synthetic protocol for making 3D MTV-COFs by balancing the linker reactivity and solvent polarity. Specifically, 15 crystalline and phase pure MTV-COF-300 isostructures are constructed by linking a tetrahedral unit with eight ditopic struts carrying various functional groups. We find that the electron-donating groups make the linker reactivity too low to allow the reaction to proceed fully, while the electron-withdrawing groups afford increased reactivity and hardly yield crystalline materials. To overcome the crystallization dilemma, the combination of polar aprotic with nonpolar solvents was used to improve the solubility of oligomers and slow the reaction kinetics in MTV-COF synthesis. We demonstrate the abilities of these MTV-COFs to tune gas dynamic behaviors and the separation of benzene and cyclohexane. These findings reveal the integration of multivariate functionalities into dynaCOFs with on-demand flexibility to achieve dynamic synergism in particular applications, outperforming their pure, monofunctional counterparts.