Multi-FPGA systems, which consist of multiple FPGAs and a printed circuit board connecting them, are useful and important tools for prototyping large scale circuits, including SoCs. In this paper, we propose a method for optimizing inter-FPGA signal transmission to accelerate the system frequency of multi-FPGA prototyping systems and shorten prototyping time. Compared with the number of I/O pins of an FPGA, the number of I/O signals between FPGAs usually becomes very large. Thus, time-multiplexed I/Os are used to resolve the problem. On the other hand, they introduce large delays to inter-FPGA I/O signals, and much lower the system frequency. To reduce the degradation of the system frequency, we have proposed a method for optimally selecting signals to be time-multiplexed and signals not to be time-multiplexed. However, this method assumes that there exist physical connections (i.e., wires on the printed circuit board) between every pair of FPGAs, and cannot handle I/O signals between a pair of FPGAs that have no physical connections between them. Thus, in this paper, we propose a method for obtaining indirect inter-FPGA routes for such I/O signals, and then combine the indirect routing method and the time-multiplexed signal selection method to realize effective time-multiplexing of inter-FPGA I/O signals on systems with various topologies.