The online documentation reflects that you can only configure up to two serial ports for simultaneous use, though the four common ports are presented as options as well as the ability to tweak their IO Base and IRQ.
http://www.virtualbox.org/manual/ch03.html#serialports
I tried to hand edit the machine definition to force the use of four ports, but it appears (at least under VBox 4.0.2) that is just ignores that section if it is not correctly specified. After opening the GUI to check what it thought, it silently removed ports 3 and 4 from my configuration and left ports 1 and 2 enabled and configured.
Your best bet (if this works with your needs) is to get a couple of USB serial controllers and let the virtual machine capture those devices and present them to the guest operating system as devices.
For what it is worth, here is the chunk of XML I used to try and configure the VM.
<UART>
<Port slot="0" enabled="true" IOBase="0x3f8" IRQ="4" hostMode="Disconnected"/>
<Port slot="1" enabled="true" IOBase="0x2f8" IRQ="3" hostMode="Disconnected"/>
<Port slot="2" enabled="true" IOBase="0x3e8" IRQ="4" hostMode="Disconnected"/>
<Port slot="3" enabled="true" IOBase="0x2e8" IRQ="3" hostMode="Disconnected"/>
</UART>